In the funded study "Developmental Insult and Brain Anomaly in Schizophrenia," we are investigating the relation of early developmental insult to adult brain disturbance among cases of schizophrenia and other schizophrenia spectrum disorders (SSD) and matched normal controls. We are bringing advanced neuroimaging and neuropsychological approaches to the assessment of adult brain disturbance, while using an epidemiological design of a large and informative birth cohort, the Prenatal Determinants of Schizophrenia cohort. The specific aims of the original study focus on: 1) the associations between SSD and disturbances in brain structure and function, and 2) their relation to early developmental insult and to familial liability. These original specific aims emphasize brain volumetric studies; neurochemical studies (neuronal integrity in prefrontal and hippocampal regions measured via n-acetyl aspartate [NAA] proton magnetic resonance spectroscopy); and neurocognitive studies (executive function/working memory and declarative memory). [unreadable] [unreadable] The purpose of this supplemental application is to significantly expand the scope of these specific aims and to support an enhanced and more sophisticated, state-of-the-art approach to the neurocognitive assessment of study subjects as well as the performance of additional measures and analyses on the functional neuroimaging data. Specifically, this supplement will support: [unreadable] [unreadable] 1. An expanded neurocognitive battery, as well as the intense data gathering, processing and analysis required for evaluation of Neurocognitive Processing Efficiency indices that examine the contributions of a singular underlying deficit ("cognitive dysmetria and ataxia") to the neuropsychological dysfunction in schizophrenic cases compared to healthy matched controls. (It will also permit a slight expansion of the total sample size to increase the power of these supplemental analyses). [unreadable] [unreadable] 2. Additional functional neuroimaging measurements of NAA in cerebellum and thalamus in order to assess neuronal integrity in key brain regions of cortico-cerebello-thalamic circuits. [unreadable] [unreadable] 3. An examination of the relationship between the Neurocognitive Processing efficiency indices and [unreadable] neuroimaging measures, to supplement the previously planned correlational analyses between individual cognitive measures and imaging regions. This relatively new approach promises to yield more integrative, stable results than are possible with older analytic techniques that focus on separate and individual cognitive and neuroimagin 9 measures. [unreadable] [unreadable]